Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the last 10 years, there has been an explosion of interest in homocysteine, a sulfur-containing amino acid that occupies a central location in the metabolic pathways of thiol compounds. This interest is primarily because of the realization that hyperhomocysteinemia is an important risk factor for vascular disease, including stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Since elevated homocysteine levels can often be normalized by supplementing the diet with folic acid (folate), pyridoxine hydrochloride (vitamin B(6)), and cyanocobalamin (vitamin B(12)), these observations raise the exciting possibility that this inexpensive and well-tolerated therapy may be effective in decreasing the incidence of vascular disease. In addition to its association with cerebrovascular disease, homocysteine may play a role in neurodegenerative disorders, even if only as a marker of functional vitamin B(12) deficiency. Homocysteine is also important to neurologists since most anticonvulsants raise homocysteine levels, an effect that may explain the teratogenic effects of these drugs. Practical knowledge concerning some details of homocysteine metabolism, the diagnosis of hyperhomocysteinemia, and the use of polyvitamin therapy to lower homocysteine levels will be increasingly important in the treatment of patients with neurologic disease. Arch Neurol. 2000;57:1422-1428
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PMID:Homocysteine and neurologic disease. 1103 Jul 93

Death with functioning graft, the most frequent cause being cardiac death, continues to be the most frequent cause of long-term graft loss. The risk of cardiovascular death in the transplanted patient is lower than in patients with other modalities of renal replacement therapy, but continues to be substantially higher than in the general population. Amongst the factors predicting patient and graft survival are hypertension, dyslipidemia, smoking and possibly hyperhomocysteinemia. It is concluded that lowering of blood pressure to levels far lower than levels accepted in the past, more widespread administration of statines, cessation of smoking and possibly administration of folate should reduce cardiovascular mortality and possibly also influence chronic allograft vasculopathy.
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PMID:Atherosclerotic complications after renal transplantation. 1111 54

Chronic haemodialysis patients have a disproportionately high risk for developing cardiovascular disease, which can only in part be explained by known risk factors such as dyslipidaemia, hypertension, hyperhomocysteinemia, diabetes mellitus and chronic volume expansion. A possible cause is that the haemodialysis treatment itself contributes to the accelerated atherosclerosis, observed in these patients. Nowadays, atherosclerosis is considered an inflammatory process, mediated by a dysfunction of the vascular endothelium. As a result, blood cells adhere to the vascular surface and release a variety of vasoactive mediators, cytokines, growth factors and free radicals. Due to the contact between blood and dialyzer, humoral systems and cellular elements are stimulated, and this may be viewed as an inflammatory reaction. As a consequence of this, the vascular surface of haemodialysis patients is repeatedly exposed to the influences of cytokines, coagulation products, vasoactive mediators, stimulated leukocytes and thrombocytes, and oxidative stress. It is therefore conceivable that the haemodialysis treatment itself enhances the greatly increased cardiovascular risk in chronic haemodialysis patients.
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PMID:[Proatherogenic changes induced by hemodialysis; probably a result of bio-incompatibility]. 1119 88

The vascular endothelium is the primary site of dysfunction in many diseases, particularly cardiovascular disease. A variety of risk factors, including smoking, hypercholesterolemia, hyperhomocysteinemia, hypertension, and diabetes mellitus, adversely affect endothelial function. Emerging evidence suggests an important role of dietary factors in modulating endothelial function. In particular, n-3 fatty acids, antioxidant vitamins (especially vitamins E and C), folic acid, and L-arginine appear to have beneficial effects on vascular endothelial function, either by decreasing endothelial activation or by improving endothelium-dependent vasodilation in patients at high risk of cardiovascular disease as well as in healthy subjects. These effects may serve as one potential mechanism through which these nutrients reduce the risk of cardiovascular disease, as observed in epidemiologic studies and several clinical trials. This article reviews clinical and experimental evidence regarding the role of these nutrients in modulating endothelial function and their potential to prevent cardiovascular disease.
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PMID:Dietary modulation of endothelial function: implications for cardiovascular disease. 1127 41

Placental abruption is due to the rupture of the uterine spiral artery. The placenta separates totally or partially from the uterine wall during pregnancy. This serious syndrome has a great risk for the mother (shock and disseminated intravascular coagulation) and her child (mortality or morbidity). To the known risk factors like hypertension, the use of cocaine and smoking, homocysteine is recognized as an independent risk factor for vascular disease and endothelial dysfunction. In contrast to normal pregnancy where the spiral artery endothelium is replaced by trophoblast, the endothelium persists in case of placental abruption. In 165 women with placental vasculopathy and 139 matched controls hyperhomocysteinemia resulted in an odds ratio of 4.7 (95% CI: 1.6-14.0). The C677T mutation gave a risk of 2.5 (95% CI: 1.0-6.0). Even up to 2 or 3 years post-partum evidence could be found of endothelial dysfunction. The combination of hyperhomocysteinemia and thrombotic factors like APC resistance, Protein-C, Protein-S, antithrombin and factor V Leiden increases the risk of placental abruption 3-7 times. The common denominator of the effect of homocysteine on blood vessels could be sited in the process of proliferation of cells that need proper methyl groups for proper function (DNA synthesis and expression). These methyl groups are delivered by D-adenosylmethionine formed from methionine after remethylation of homocysteine. The coagulation factors and plasma homocysteine values can be modulated by vitamins, folic acid and folates in particular. To prove the clinical value of folate supplementation placebo-randomized trials are urgently needed: for placebo to be started after the period of neural tube closure.
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PMID:Clotting disorders and placental abruption: homocysteine--a new risk factor. 1130 Nov 73

The past decade has witnessed enormous progress in our understanding of the nature of this process. The development of an atherosclerotic plaque is a complex process which begins with endothelial dysfunction, the trigger for which are factors such as hypercholesterolemia, smoking, hypertension, hyperhomocysteinemia and impaired glucose metabolism. This dysfunction includes increased endothelial permeability to lipoproteins and other plasma constituents, which is mediated by NO, PDGF, prostacyclin, angiotensin II and endothelin; up-regulation of endothelial adhesion molecules including VCAM-1, ICAM-1, and selectins and migration of leukocytes and monocytes-macrophages in the subendothelial space mediated by oxidized LDL, MCP-1, PDGF and MCSF. The next step includes smooth-muscle cells migration (stimulated by PDGF and TGF-beta), T-cell activation (mediated by TNF-alpha and IL-2), formation of foam-cells from macrophages (mediated by oxidized LDL, MCSF, TNF-alpha and IL-1) and platelet adherence and aggregation (stimulated by thromboxane A2, tissue factor etc). The smooth muscle cells form a fibrous cap which confers mechanical stability of the plaque and separates the lipid rich thrombogenic core from the lumen and circulating blood. Whether a plaque will remain intact and therefore stable or rupture and lead to thrombosis causing an acute coronary syndrome (MI, unstable angina pectoris) depends upon a number of factors, the most important of which is its composition. Plaque size plays only a minor role in determining risk of an acute coronary syndrome. Rupture of the fibrous cap occurs due to thinning of the cap caused by an influx and activation of macrophages which release metalloproteinases and other proteolytic enzymes (stimulated by inflammatory cells, particularly T-lymphocytes). These enzymes cause degradation of the fibrous tissue of the cap which can result in thrombous formation and occlusion of the artery. Stable plaques have a thick fibrous cap, a small lipid core, and few inflammatory cells. In contrast, vulnerable plaques have a high lipid content, numerous inflammatory cells, and a thin fibrous cap with reduced collagen and vascular smooth muscle cells in it. Although vulnerable plaques are believed to account for only a small number of all coronary atheromas, they are responsible for most acute coronary events.
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PMID:[New information on the pathophysiology of atherosclerosis]. 1137 94

Stroke is a major cause of morbidity and mortality. Risk factors for stroke have been determined through prospective epidemiologic study. Control of risk factors has been demonstrated to reduce stroke incidence, either through controlled trials or inferred from observational studies. In the past few years, new approaches to the treatment of established risk factors have been discovered. These include aggressive control of hypertension in diabetes patients, prevention of type 2 diabetes through lifestyle modification, carotid endarterectomy for moderate symptomatic carotid stenosis, encouragement of a high level of physical activity, and control of abdominal obesity and elevated body mass index. In addition, new strategies for stroke prevention have been identified, including encouragement of a diet high in fruits, vegetables, whole grains, and omega-3 fatty acids, the use of vitamins B12, B6, and folic acid in hyperhomocysteinemia, and moderate alcohol consumption. Clinical trial data support the use of hydroxy-methyl-coenzyme A inhibitors in patients with coronary artery disease, and ramipril in high-risk patients with coronary artery disease and diabetes, for the primary prevention of stroke. New risk factors for stroke are being investigated, including the role of chronic inflammation and infection, and these may provide future strategies for stroke prevention.
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PMID:Prevention of strokes. 1138 98

This paper reviews the biochemical and physiological data underlying hyperhomocysteinemia. Elevation of plasma homocysteine arises from disrupted of its metabolism (remethylation to methionine and transsulfuration to cystathionine) and is a function of a complex interaction between multiple genetic and environmental factors. Hyperhomocysteinemia, a conditions that recent epidemiological studies have shown to be associated with an increased risk of vascular diseases, may be a equal importance to hypercholesterolemia, hypertension and smoking in etiology of atherosclerosis. Based on the role of folic acid, vitamin B12 and B6 in homocysteine metabolism supplementation with these vitamins in treatment of hyperhomocysteinemia both in cardiovascular diseases and neural tube defects is reviewed.
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PMID:[Homocysteine and hyperhomocysteinemia]. 1139 9

Peripheral arterial disease affects approximately 8-10 million people in the United States. Approximately one-third to one-half of these individuals are symptomatic. The risk factors that contribute to peripheral arterial disease are similar to those associated with other forms of atherosclerosis, including diabetes mellitus, cigarette smoking, hypercholesterolemia, high blood pressure, and hyperhomocysteinemia. Of these, diabetes and cigarette smoking pose the greatest risk for developing peripheral arterial disease. The prognosis of patients with these risk factors is limited because of their greater risks for myocardial infarction, stroke, and cardiovascular death. Cardiovascular mortality correlates inversely with the ankle/brachial index, and the risk of death is greatest in those with the most severe peripheral arterial disease. Treatment regimens to reduce cardiovascular morbidity and mortality in patients with peripheral arterial disease should include risk factor modification and antiplatelet therapy. The cardinal symptoms of peripheral arterial disease include intermittent claudication and rest pain, with the latter being indicative of critical limb ischemia. Therapeutic strategies that focus on improving the patient's quality of life, reducing the severity of claudication, and improving limb viability include supervised exercise training, pharmacotherapy, and revascularization. Two drugs-pentoxifylline and cilostazol-currently are approved by the Food and Drug Administration for the treatment of patients with claudication. Meta-analyses have suggested that, compared with placebo, pentoxifylline improves maximal walking distance by approximately 20-25%. Cilostazol is a phosphodiesterase type 3 inhibitor. In clinical trials, cilostazol has consistently improved maximal walking distance as compared with placebo, with the range of improvement being approximately 40-60%. Drugs that are currently under investigation include propionyl-L-carnitine, vasodilator prostaglandins, L-arginine, and the angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factors.
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PMID:Medical management of peripheral arterial disease. 1140 4

We tested if vitamin E, a fat-soluble antioxidant, prevents resistance vessel endothelial dysfunction caused by methionine-induced hyperhomocysteinemia in humans. Moderate elevations in plasma homocysteine concentrations are associated with atherosclerosis and hypertension. Homocysteine causes endothelial dysfunction possibly through several mechanisms. No previous study has tested if a fat-soluble antioxidant can prevent endothelial dysfunction caused by experimental hyperhomocysteinemia. Ten healthy subjects participated in a 2 x 2 factorial, double-blind crossover study, receiving L-methionine (100 mg/kg at -6 hours) or vehicle, with and without vitamin E (1,200 IU at -13 hours). Endothelial function of forearm resistance vessels was assessed using forearm blood flow responses to brachial artery administration of endothelium-dependent and endothelium-independent agents. Forearm resistance vessel dilatation to acetylcholine was significantly impaired 7 hours after methionine (placebo, 583 +/- 87% vs methionine 30 +/- 68%; p <0.05). Dilatation to bradykinin was also impaired (placebo, 509 +/- 54% vs methionine 289 +/- 48%; p <0.05). Methionine did not alter vasodilatation to the endothelium-independent vasodilators, nitroprusside, and verapamil. Methionine-induced impairment of resistance vessel dilatation to acetylcholine and bradykinin (p <0.05 vs placebo) was prevented by administration of vitamin E (acetylcholine, p = 0.004; bradykinin, p = 0.004; both vs methionine alone). Experimentally increasing plasma homocysteine concentrations by oral methionine rapidly impairs resistance vessel endothelial function in healthy humans and this effect is reversed with administration of the fat-soluble antioxidant, vitamin E.
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PMID:Effect of vitamin E on resistance vessel endothelial dysfunction induced by methionine. 1147 9


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